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June 19, 2006
Rats Rule, Right?
So, you're developing a drug candidate. You've settled on what looks like a good compound - it has the activity you want in your mouse model of the disease, it's not too hard to make, and it's not toxic. Everything looks fine. Except. . .one slight problem. Although the compound has good blood levels in the mouse and in the dog, in rats it's terrible. For some reason, it just doesn't get up there. Probably some foul metabolic pathway peculiar to rats (whose innards are adapted, after all, for dealing with every kind of garbage that comes along). So, is this a problem?
Well, yes, unfortunately it is. Rats are the most beloved animal of most toxicologists, you see. (Take a look at the tables in this survey, and note how highly the category "rodent toxicology" always places). More compounds have gone through rat tox than any other species, so there's a large body of experience out there. And the toxicologists just hate to go without it. Now, a lot of compounds have been in mice, for sure, but they just aren't enough of a replacement. The two rodent species don't line up as well as you'd think. And there's no other small animal with the relevency and track record of the noble rat. (People outside the field are sometimes surprised to learn that guinea pigs aren't even close - they get used in cardiovascular work, but that's about it).
So if your compound is a loser in the rat, you have a problem. You can pitch to go straight into larger animals, but that's going to be a harder sell without rat data. If your project is a hot one, with lots of expectations, you'll probably tiptoe into dog tox. But if it's a borderline one, having the rats drop out on you can kill the whole thing off. They use up a lot of compound compared to the mouse, they're more likely to bite your hand, and they're an order of magnitude less sightly. But respect the rat nonetheless.
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